Prostate growth, from normal to neoplastic, can be viewed as a change from paracrine regulation of epithelial growth to autocrine regulation (Culig et al. (1996) The Prostate 28: 392-405). Additionally, prostate cancers, especially advanced tumors, are frequently insensitive to the normal mitogenic action of growth factors, suggesting that prostate cancer expresses constitutively one or more of those genes unregulated by growth factors. The identification of genes expressed differentially in prostate cancers of dissimilar phenotypes could give clues to genes important in malignant transformation and progression. Moreover, these genes could serve as prognostic and diagnostic markers as well as new targets for therapy. However, the identification of growth regulatory genes in prostate cancer has been difficult and has lagged behind comparable studies in other cell types.
Methods to identify differentially expressed genes in other tissues have included differential screening of cDNA, libraries with selective probes, subtractive hybridization utilizing DNA/DNA hybrids or DNA/RNA hybrids, RNA fingerprinting and differential display (Mather et al. (1981) Cell 23:369-378; Hedrick et al. (1984) Nature 308:149-153; Davis et al. (1992) Cell 51:987-1000; Welsh et al. (1992) Nucleic Acids Res. 20:4965-4970; and Liang and Pardee (1992) Science 257:967-971). Recently, PCR-coupled subtractive processes have also been reported (Straus and Ausubel (1990) Proc. Natl. Sci. USA 87:1889-1893; Sive and John (1988) Nucleic Acids Res. 16:10937; Wieland et al. (1990) Proc. Natl. Acad. USA 87:2720-2724; Wang and Brown (1991) Proc. Natl. Acad Sci. USA 88:11505-11509; Lisitsyn et al. (1993) Science 259:946-951; Zing et al. (1994) Nucleic Acids Res. 22:4381-4385; Hubank and Schak (1994) Nucleic Acids Res. 22:5640-5648). Each of these methods has achieved some success but each has some inherent limitations. For example, problems associated with differential display include identification of "false positives, " redundancy, and under-representation of certain mRNA species. Liang and Pardee (1992) Science 257:967-971. In addition, cDNA-RDA (Hubank and Schatz (1994) Nucleic Acids Res. 22:5640-5648; Lisitsyn et al. (1993) Science 259:946-951) is a labor-intensive process, and its efficiency remains to be evaluated. Some advances have been made in isolating genes expressed preferentially in prostate cancer versus normal tissue (Shen et al. (1995) PNAS USA 92:6778-6782; Wang et al. (1996) Cancer Res. 56:3634-3637; Liu et al. (1997) The Prostate 30:145-153). Less data exist regarding differential expression of novel genes in human prostate cancers of different growth and metastatic potential (Blok et al. (1995) The Prostate 26:213-224).
Thus, a need still exists to develop a more efficient method for identification of differentially expressed genes and differences in genomic sequences.
Accordingly, an object of the invention is to provide a differentially expressed gene isolated by the methods described herein.